This project employs the H (histocompatibility) system of the mouse to detect spontaneous and environmentally induced mutations. The H system comprises by definition those genes on which the acceptance and rejection of orthotopically placed tail-skin grafts depends. Not less than 29 and perhaps some hundreds of loci are monitored at one time. In a trial, either the C57BL/6 or the BALB/c parent is treated, and the Fl progeny are H-tested. From the pattern of graft acceptance and rejection, suspected mutant F1s are detected that show a gain, a loss, or a gain plus loss in antigenicity. Proof of mutation is obtained by backcrossing the suspect and demonstrating incompatibility in the progeny. Currently, a large-scale trial with x rays is in progress (O to 800 rads, single and split doses). This is to be followed by trials with chemicals. The H genes differ greatly in function from those of the 7-locus test of radiation genetics. Results with the H test should therefore be of independent, comparative, and supplementary value.